Endocrine Part 2 Hyper/HypoCa, Osteo, Pituitary

Question 1

Calcium Metabolism and Bones Diseases

(3)

Answer 1

Hypercalcemia

Hypocalcemia

Osteoporosis

Question 2

Hypercalcemia

Common medical condition

• Symptomatic?
• Severe hypercalcemia is potentially _____
• (2) causes, effective Rx is often possible–accurate diagnosis is key to definitive treatment

Answer 2

• Often asymptomatic (most often found on a Chem panel)
• Severe hypercalcemia is potentially fatal
• Hyperparathyroidism vs. Cancer Effective Rx is often possible–accurate diagnosis is key to definitive treatment

Hypercalcemia more important is the work up than the treatment

Question 3

Hypocalcemia

Relatively rare

• Symptomatic?
• Seen in both _____ and ____ practice
• Causes (2) - Accurate diagnosis is key to definitive treatment

Answer 3

• May be severely symptomatic
• Seen in both pediatric and adult practice
• Hypoparathyroidism vs. Non-PTH deficient Hypocalcemia - Accurate diagnosis is key to definitive treatment

Hypocalcemia treat first then work up

Question 4

Calcium Labs

(1) 50%

(1) 40%

(1) 10%

Answer 4

Ionized Ca++

Albumin (bound calcium)

Organic complexes (citrate, phosphate)

Corrected serum Ca⁺⁺= total serum Ca⁺⁺ (mg/dL) + 0.8X (4.0- serum albumin{g/dL})

If albumin is low, can underestimate total serum Ca

Question 5

pH Effects on Calcium

Acidosis =

Alkalsosis =

Answer 5

Acidosis increases Ca

Alkalosis decreases ionized calcium (hyperventilation → alkalosis, symptoms of tetany)

Question 6

Parathyroid Hormone Regulates Calcium

PTH effect on the

1. Gut =
2. Kidneys =
3. Bones =

Answer 6

1. Forms “active” Vitamin D to increase gut Ca2+ absorption
2. Stimulates calcium reabsorption and phosphate excretion in the kidney
3. Osteoblast stimulation which increases bone resorption of calcium

• Parathyroid glands cannot be palpated bc sit behind thyroid*
• 3 things that happen we have a low serum calcium*

Question 7

Vitamin D regulates Ca Absorption

Sources of vitamin D: fortified ____, ___ oils, Rx (2)

Vitamin D absorbed from the skin and gut are stored in the ____

PTH effect on Vitamin D?

What Vitamin D do we measure in primary care?

Answer 7

Fortified milk, Fish oils, D2 ergocalciferol, D3 cholecalciferol

Vitamin D stored in the liver

PTH activates the inactivated form of Vit D to its active form - 25 OH Vit D → 125 OH Vit D

We measure the storage form of Vitamin D in primary care

Question 8

Manifestations of Hypercalcemia

Hypercalcemia favors membrane hyperpolarization → _____ excitability

(2)*

Neurologic: fatigue, ___ness, con____, coma

Gastrointestinal: C_______, abdominal pain, peptic ulcers

Renal: ____uria, de_____, nephro______

Cardiac: palpitations, arrhythmia, _____cardia, _____ QT, AV block

Answer 8

Hypercalcemia favors membrane hyperpolarization → reduced excitability

Lethargy, Coma*

Neurologic: fatigue, weakness, confusion, coma

Gastrointestinal: Constipation, abdominal pain, peptic ulcers

Renal: Polyuria, dehydration, nephrolithiasis

Cardiac: palpitations, arrhythmia, bradycardia, short QT, AV block

Question 9

Clinical Manifestations of Hypercalcemia

Vicious cycle of severe hypercalcemia =

Anything above ___ mg/dL is an emergency! and requires (1)

Anything under ___mg/dL is not concerning, will start to see symptoms when it rises above this level

First treatment will be (1)

Answer 9

Hypercalcemia causes osmotic diuresis → reduced GFR → polyuria/n/v → dehydration → hypercalcemia

>13mg/dL is an emergency! requires inpatient eval

<12 not concerning, >12 will start to see sx

HYDRATION

Question 10

Differential Diagnosis for Hypercalcemia

The most important test is repeat Ca and draw serum PTH

PTH Mediated (1)* - and what will the labs show?

Non-PTH Mediated (1)* - and what will the labs show?

Answer 10

Primary Hyperparathyroidism - High Ca and High PTH

Malignancy (non-PTH mediated - humoral, lytic, vitD and/or cytokine production) - High Ca but Low PTH → refer

Question 11

Primary Hyperparathyroidism

• PHPT is the ____ common cause of hypercalcemia, affecting 1/1000 persons (more with increased age)
• Most patients with hyperparathyroidism are ______ at diagnosis
• (2) lab values is generally diagnostic of PHPT

Answer 11

• PHPT is the most common cause of hypercalcemia, affecting 1/1000 persons (more with increased age)
• Most patients with hyperparathyroidism are asymptomatic at diagnosis
• Elevated or unexpectedly “normal” PTH + Elevated albumin adjusted Ca level lab values is generally diagnostic of PHPT

PHPT also concerning bc of kidney stones

Question 12

Primary Hyperparathyroidism Lab and Imaging Eval

• Serum C_____
• P______ hormone
• 25 OH _______
• G______ filtration rate
• Bone d_______
• (1) imaging to detect stones

Answer 12

• Serum Calcium
• Parathyroid hormone
• 25 OH Vitamin D
• Glomerular filtration rate (check kidneys!)
• Bone density
• Ultrasound to detect stones

Question 13

Primary Hyperparathyroidism Treatment

(1) recommended for pts <50yo with clinically significant hypercalcemia, osteoporosis or fragility fracture, renal calculi, hypercalciuria, impaired renal function

Medical Management

• correction of dietary (1) and (1) deficiency
• Rx (1) lowers serum calcium levels
• Rx (1) improves bone density, but reducing fracture risk unknown

Answer 13

Surgery <50 + significant hypercal

• Correction of dietary calcium and vitamin D deficiency
• Calcinet
• Bisphosphonates

If pts <50 yo we generally treat definitively by surgical resection

• If >50 and asymptomatic – wait and watch*
• -Tell them to don’t avoid Ca completely – to prevent driving up Ca-**Get bone density and urine tests every few years*

Question 14

When to Asymptomatic Primary Hyperparathyroidism

Once you find someone with high PTH after presenting with hypercalcemia – get these tests

(2)-(2),(3)

Answer 14

Skeletal

• DEXA for bone mineral density
• Xray/CT/MRI/VFA for vertebral fracture

Renal

• CrCl <60ml
• 24h urine for calcium >400 and increased stone risk
• Xray/US/CT for nephrolithiasis

Question 15

PHPT Treatment

1. Surgical (1)
2. Medical
   
   1. Ob_____: maintain hy____, avoid diu______, get (1) to monitor for osteoporosis and treat it
   2. What to do about dietary calcium?
   3. (1)Rx activates CaSR and inhibits PTH secretion

Answer 15

1. Surgical removal of overactive parathyroid gland (localization using neck US, sestamibi scan)
2. Medical
   
   1. Observation, maintain hydration, avoid diuretics, get DEXA scan to monitor for osteoporosis
   2. NO NEED TO LIMIT DIETARY CALCIUM
   3. Cinacalcet activates CaSR and inhibits PTH secretion

• Tx for osteoporosis – give bisphosphonates*
• Cinacalcet (lowers PTH) and bisphosphonate given if cannot have surgery*
• Critically important is to maintain hydration to avoid vicious cycle of kidney injury*

Question 16

Non-PTH mediated Hypercalcemia Causes

M______ - often advanced, poor prognosis

(1) mediated - increased gut absorption

Answer 16

Malignancy

Vitamin D mediated

Question 17

Malignancy Non-PTH mediated Hypercalcemia

1. ______ hypercalcemia of malignancy - PTHrP
   
   1. 80% of cases, mostly _____ cancers (cervix, lung, head, and neck)
2. Local osteo_____ lesions - bone ____
   
   1. 20% of cases - br_____ ca, pr______ ca, multiple _____
3. 1,25OH2-vit D mediated
   
   1. <1% - ly_______

Answer 17

1. Humoral hypercalcemia of malignancy - PTHrP
   
   1. 80% of cases, mostly squamous cancers (cervix, lung, head, and neck)
2. Local osteolytic lesions - bone mets
   
   1. 20% of cases - breast ca, prostate ca, multiple myeloma
3. 1,25OH2-vit D mediated
   
   1. <1% - lymphoma

Question 18

Vitamin D mediated - Non PTH Hypercalcemia

1. (1) intoxication – excess 25-OH-vitamin D levels
2. (1) mediated – excess 1,25-OH-vitamin D
   
   1. Granulomatous Disease – Sarcoid, Crohn’s disease, Tb
   2. Lymphoma

Answer 18

1. Vitamin D intoxication – excess 25-OH-vitamin D levels
2. Calcitriol mediated – excess 1,25-OH-vitamin D
   
   1. Granulomatous Disease – Sarcoid, Crohn’s disease, Tb
   2. Lymphoma

Question 19

Treatment of Hypercalcemia

1. Treat the underlying p______
2. Enhance _____ calcium excretion
3. Block ______ activity
4. Block ______ calcium absorption

How?

Answer 19

1. Treat the underlying pathophysiology
   
   1. ie surgery for PHPT
2. Enhance renal calcium excretion
   
   1. Volume expansion promotes calciuresis: saline, then loop diuretics (no thiazides)
   2. Dialysis against low calcium bath (if CA <18mg/dL)
3. Block osteoclastic activity
   
   1. Pamidronate/Zoledronate (IV bisphosphonates
4. Block intestinal calcium absorption
   
   1. Low calcium diet, avoid calcium supplements, glucocorticoids if Vit D mediated

Question 20

Response to Hypocalcemia

Answer 20

Question 21

Clinical Manifestations of Hypocalcemia

Hypocalcemia favors membrane depolarization (Na+ channel effects) → ______ excitability

(2) signs, Se_______

• Neurologic: t______, B_____ reflexes, Ch______ isgn, se______
• MSK: muscle ______, T______ sign, carpopedal sp______, t_____*
• Cardiac: _____ QT, arrhythmia

Any of these S/S/ Ca

Answer 21

Increased excitability

Chvostek’s and Trousseau’s sign, Seizures

• Neurologic: tingling, brisk reflexes, Chvostek’s sign, seizures
• Musculoskeletal: muscle cramps, Trousseau’s, carpopedal spasm, tetany
• Cardiac: long QT, arrythmia

S/S, Ca <8.5 → ER

• Chvostek’s = tapping on facial nerve → cheek will twitch*
• Trouseau’s (Pic)*

Question 22

Differential Diagnosis of Hypocalcemia

(2) (2), (2)

Answer 22

Hypoparathyroid (PTH low, Phos high)

1. Genetic
2. Acquired

Non-PTH deficient (PTH elevated, Phos variable)

1. Chronic Kidney Disease
2. Vitamin D deficiency or resistance

Question 23

Genetic vs. Acquired Hypoparathyroidism

What is the most common cause of hypoparathyroidism?

1. Genetic
   
   1. ____immune (polyglandular syndrome type 1)
   2. Parathyroid dev_______ (22g deletion = DiGeorge syndrome, TBX1, GCM2)
2. Acquired
   
   1. Post (1) ~75%
   2. M_____ deficiency (alc, mag wasting meds, diarrhea etc)
   3. H_____ bone syndrome (post parathyroidectomy for PHPT)
   4. (1) inhibitors

Answer 23

Post neck surgery ~75%

1. Genetic
   
   1. Autoimmune (polyglandular syndrome type 1)
   2. Parathyroid development (22g deletion = DiGeorge syndrome, TBX1, GCM2)
2. Acquired
   
   1. Post neck surgery ~75%
   2. Magnesium deficiency (alc, mag wasting meds, diarrhea etc)
   3. Hungry bone syndrome (post parathyroidectomy for PHPT)
   4. Immune checkpoint inhibitors

Magnesium deficiency – decreases function of PTH

Question 24

Differential Diagnosis of Hypocalcemia Chart

Takeaway - Check (4)

Answer 24

PTH, PO4, Mg, Cr or EGFR

Question 25

Treatment of Hypocalcemia **_For Acute, Symptomatic Hypocalcemia_** **(1)** followed by **(1)** Once normalized? **_For Hypoparathyroidism_** **(2)** supplements for a goal calcium LLN + Monitor **(1) urine calcium and sx**

Answer 25

**_For Acute, Symptomatic Hypocalcemia_** **Rapid IV Ca++** followed by **Oral supplements** Once normalized, it is then important to differentiate between PTH-deficient and non-PTH-deficient causes to determine treatment strategy **_For Hypoparathyroidism_** **Calcitrol (1,25 OH Vitamin D)** supplements for a goal calcium LLN + **Monitor 24 urine calcium and sx**

Question 26

Calcium Metabolism - Bone - A Dynamic Organ (1) buildup bone (1) breakdown bone These processes should happen \_\_\_\_\_\_, over time less ____ and more breakdown Any breakdown in any of these steps → _______ will develop (low bone ____ + low bone \_\_\_\_\_)

Answer 26

Osteoblasts buildup bone Osteoclasts breakdown bone (bone resorption) These processes should happen together, over time less pairing and more breakdown Any breakdown in any of these steps → osteoporosis will develop (low bone mass + low bone quality)

Question 27

Calcium Metabolism-Bone ## Footnote **Which type of bone is very sensitive to PTH excess?** **Which type of bone is very sensitive to glucocorticoids?**

Answer 27

**Cortical Bone** (wrist \> hip \> vertebrae) **Cancellous Trabecular Bone** (vertebrae \> hip \> wrist)

Question 28

Osteoporosis Definitions ## Footnote **Clinical Definition** **DEXA Definition**

Answer 28

Poor bone strength (density + quality) T score \> -2.5 SD below the mean for young adults

Question 29

Osteoporosis Patho * Systemic skeletal disease characterized by low bone _____ and m\_\_\_\_architectural deterioration of bone tissue (q\_\_\_\_\_) * Bone Quality – m\_\_\_architecture, m\_\_\_\_architecture, microdamage accumulation, degree of m\_\_\_\_\_ization, rate of bone t\_\_\_\_\_\_ * Consequently – there is an increase in bone fr\_\_\_\_\_ and risk of fr\_\_\_\_\_

Answer 29

* Systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue (quality) * Bone Quality – macroarchitecture, microarchitecture, microdamage accumulation, degree of mineralization, rate of bone turnover * Consequently – there is an increase in bone fragility and risk of fracture

Question 30

Peak Bone Mass and Rate of Bone Loss * Intrinsic Factors * G\_\_\_\_\_, wnt pathway * Extrinsic Factors * Es\_\_\_\_\_ Status * XRC/Nu\_\_\_\_\_ * Tob\_\_\_\_\_ * Ca\_\_\_\_/Vitamin __ status * Ch\_\_\_\_ Diseases * Med\_\_\_\_\_\_

Answer 30

* Intrinsic Factors * Genes, wnt pathway * Extrinsic Factors * Estrogen Status * XRC/Nutrition * Tobacco * Calcium/Vitamin D status * Chronic Diseases * Medications

Question 31

Secondary Osteoporosis Due to Systemic Diseases 1. Endocrine (3) 2. Oncologic (1) 3. Nutritional Disorders (1) 4. Inflammatory Arthritis (1) 5. Medications associated with OP (2)

Answer 31

1. **Hypogonadism (Hyperprolactinemia), Cushing's, Primary Hyperparathyroidism** 2. **Multiple Myeloma** 3. **Celiac sprue** 4. **Rheumatoid Arthritis** 5. **Glucocorticoids, PPI's**

Question 32

**Prevalence of Osteoporosis and Incidence of Fracture** * Half of \_\_\_yo have osteoporosis* * Most common fracture is radiographic asymptomatic _______ fracture* * We worry most about ___ fracture → decreased QOL, increased mortality*

Answer 32

* Half of 80yo have osteoporosis* * Most common fracture is radiographic asymptomatic vertebral fracture* * We worry most about hip fracture → decreased QOL, increased mortality*

Question 33

Risk Factors for Fracture **Major Risk Factors** * Personal _____ of fracture as an adult * History of fragility fracture in a first (1) * ____ body weight * Current sm\_\_\_\_\_\_ * Use of oral (1) therapy (daily dose equivalent, _\>_ 5mg of prednisone) for more than 3m **Additional Risk Factors** * Impaired v\_\_\_\_\_ * Es\_\_\_\_\_\_\_ deficiency at an early age (before 45y) * Poor health or fr\_\_\_\_\_ * Recent f\_\_\_\_\_ * Low C\_\_\_\_\_ intake (lifelong) * Low physical ac\_\_\_\_\_ * Al\_\_\_\_\_ in amounts greater than 2 drinks per day

Answer 33

**Major Risk Factors** * Personal history of fracture as an adult * History of fragility fracture in a first degree relative * Low body weight * Current smoking * Use of oral corticosteroids therapy (daily dose equivalent, _\>_ 5mg of prednisone) for more than 3m **Additional Risk Factors** * Impaired vision * Estrogen deficiency at an early age (before 45y) * Poor health or frailty * Recent falls * Low Calcium intake (lifelong) * Low physical activity * Alcohol in amounts greater than 2 drinks per day

Question 34

Osteoporosis Treatment Most common med **(1)** Only one that promotes bone formation **(1)** Lifestyle measures = adequate weight _____ exercises, _____ cessation, avoid excess _____ intake, (2) supplements

Answer 34

**Bisphosphonates** (Risedronate) **PTH hormone\*** Adequate weight bearing exercises, smoking cessation, avoid excess alcohol, Calcium supplementation, Vitamin D

Question 35

Bisphosphonates * Bind “av\_\_\_\_\_” to hydroxyapatite crystal * Impair osteo\_\_\_\_\_-mediated bone resorption–“anti-\_\_\_\_\_” * Enhance osteoclast ap\_\_\_\_\_ * Orals: poorly absorbed, risk of esoph\_\_\_\_\_\_ * IV: can cause “\_\_\_ like reaction” * Contraindicated if ____ \< 30-35%

Answer 35

* Bind “avidly” to hydroxyapatite crystal * Impair osteoclast-mediated bone resorption–“anti-resorptive” * Enhance osteoclast apoptosis * Orals: poorly absorbed, risk of esophagitis * IV: can cause “flu like reaction” * Contraindicated if GFR \< 30-35% *Must drink with full glass of water and nothing else*

Question 36

How well do Bisphosphonates reduce fracture risk?

Answer 36

70% risk reduction

Question 37

**MOAB that blocks osteoclast activation** **Reduces fracture risk by?** Route = Concern =

Answer 37

**Denosumab\*** **68% risk reduction** Subq injection If patient stops abruptly, will experience acute loss of bone in SPINE

Question 38

Rare complication that happens with recurrent IV treatment of Bisphosphonates

Answer 38

Osteonecrosis of the Jaw

Question 39

Rare complication that occurs with long term use of bisphosphonates

Answer 39

Atypical Femur Fracture Happens distal to lesser trochanter to just proximal to supracondylar flare No or minimal trauma, complete or incomplete Minor features: prodromal pain, cortical thickness, periosteal reaction

Question 40

Bisphosphonate rare SE vs. osteoporosis fracture How often do these atypical fractures occur? Is it worth it to take a bisphosphonate?

Answer 40

Bottom line – your more likely to suffer a osteoporosis fracture than a SE risk fracture – these meds are very very safe

Question 41

Metabolic Bone Disease - Estrogen/HRT Effects on Hip fractures/osteoporosis?

Answer 41

Estrogen/HRT reduces risk of Hip fractures

Question 42

**Calcium Metabolism - The role of Vitamin D** How does Vitamin D deficiency effect calcium? Preferred range for Serum 25OHD stores? (1) enhances intestinal calcium transport 45-65% Intestinal ______ transport increases to 80%

Answer 42

Vitamin D deficiency → poor absorption of calcium (10-15) and phosphorus 30-60ng/mL 1,25 OHD enhances intestinal calcium transport (45-65%) Intestinal phosphorus transport increases to 80% *Bones cannot calcify, will become weak*

Question 43

What imaging modality is used to visualize the pituitary? pic = saggital view

Answer 43

**Sella Protocol** **MRI** - Fine pituitary cuts *(group of MRI sequences put together to improve sensitivity and specificity for the assessment of lesions* *of the pituitary gland)* pic = coronal view

Question 44

What hormone is in excess in these pictures of twins?

Answer 44

Excess growth hormone = gigantism

Question 45

**Growth Hormone Excess S/S** GF/IGF-1 effects - dependent on hormone levels 1. Ac\_\_\_ changes and soft tissue \_\_\_\_growth 2. Musculoskeletal involvement 1. Prognathism = 2. **Jaw Mal\_\_\_\_\_\_** 3. Frontal B\_\_\_\_\_ 4. Proximal myopathy 3. Visceromegaly 1. **T\_\_\_\_\_\_**, prostate, thyroid, salivary glands, liver, spleen, kidney 4. Skin - H\_\_\_\_hydrosis 5. Cardiovascular 1. Arrythmia, H\_\_\_\_tension and valvular heart disease (~60%) 2. Concentric myocardial hypertrophy can lead to diastolic _____ **heart \_\_\_\_\_** 6. Entrapment Neuropathy 1. Median nerve - **(1) syndrome (can be bilateral)**

Answer 45

1. Acral changes and soft tissue overgrowth 2. Musculoskeletal involvement 1. Prognathism = protruding of lower jaw 2. **Jaw Malocclusion** 3. Frontal Bossing 4. Proximal myopathy 3. Visceromegaly 1. **Tongue**, prostate, thyroid, salivary glands, liver, spleen, kidney 4. Skin - Hyperhydrosis 5. Cardiovascular 1. Arrythmia, Hypertension and valvular heart disease (~60%) 2. Concentric myocardial hypertrophy can lead to diastolic **congestive** **heart failure** 6. Entrapment Neuropathy 1. Median nerve - **carpal tunnel syndrome (can be bilateral)**

Question 46

Growth Hormone Excess S/S GH/IGF-1 Effects -dependent on hormone levels **(1)** effect on joints **(2)** effects on pulmonary **(1)** effect on endocrine **(2)** local tumor mass effects **Mortality due to C\_\_\_\_\_\_, R\_\_\_\_\_ disease and C\_\_\_\_ Cancer**

Answer 46

**Arthritis** **Obstructive or Central Sleep Apnea** **Diabetes mellitus\*** **Headaches, Visual field deficits** **Cardiovascular, Respiratory disease, Colon Cancer**

Question 47

**70% of acromegaly is secondary to a (1)**

Answer 47

**Benign Pituitary Macroadenoma**

Question 48

**Acromegaly Diagnostic Labs** ## Footnote **(2) Tests\***

Answer 48

**IGF-1 Level\*\*** **GH Glucose Suppression Testing -** Glucose fails to suppress growth hormone in acromegaly

Question 49

Growth Hormone Excess - Confirming the Diagnosis

Answer 49

Question 50

Growth Hormone Excess Treatment Goals **Remove the \_\_\_\_\_\_** **\_\_\_\_\_\_\_ GH secretion** **Preserve the ______ function**

Answer 50

**Remove the adenoma** **Normalize GH secretion** **Preserve the pituitary function**

Question 51

GH Excess Treatment **S\_\_\_\_\_\_, R\_\_\_\_\_ therapy** **S\_\_\_\_\_\_ analogues** **(1) antagonist, (1) agonist**

Answer 51

**Surgery , Radiation therapy** **Somatostatin analogues** **GH Rec antagonist, Dopamine agonists** * If pituitary tumor confirmed -\> then surgery* * If surgery not fully effective can add on medical tx like meds/RT*

Question 52

Prolactin Regulation **\_\_\_\_\_ inhibits prolactin** Hyperprolactinemia presents in women with O\_\_\_\_menorrhea A\_\_\_\_horrea, or G\_\_\_\_\_\_hea syndrome

Answer 52

**Dopamine inhibits prolactin** (dopamine goes down after pregnancy so mother can secrete breast milk) Hyperprolactinemia presents in women with Oligomenorrhea Amenhorrea, or Galactorrhea syndrome

Question 53

Causes of Hyperprolactinemia ## Footnote **(1) most common cause** **(1) Rx**

Answer 53

**Microadenomas and Macroadenomas** (tumor secreting its own prolactin is most common cause) ## Footnote **Anti-Dopaminergics**

Question 54

Patho of Hyperprolactinemia **Prolactinomas present with \_\_\_\_\_\_** Increase in prolactin _____ (1) which then _____ (2) **(3)\* effects**

Answer 54

**Prolactinomas present with Hypogonadism** Increase in prolactin suppresses GnRH which then suppresses LH, FSH **Amenhorrhea** **Infertility** **Impotence**

Question 55

Male Clinical Manifestations of Hyperprolactinemia Hyperprolactinemia is a cause of Hypogonadotropic Hypogonadism – (central or secondary hypogonadism) * Low T\_\_\_\_\_\_\_ with normal or low LH/FSH * **Decreased l\_\_\_\_\_** – impotence * Delayed diagnosis – macroadenoma more common * **Inf\_\_\_\_\_ (less common)** * **\_\_\_ Bone Mass/(1)**\*

Answer 55

* Low Testosterone with normal or low LH/FSH * **Decreased libido** – impotence * Delayed diagnosis – macroadenoma more common * **Infertility (less common)** * **Low Bone Mass/Osteoporosis**\*

Question 56

Female Clinical Manifestations of Hyperprolactinemia * **(2)orrhea** with normal or low LH/FSH * **G\_\_\_\_\_orrhea** * Decreased l\_\_\_\_\_ - sexual dysfunction * Inf\_\_\_\_\_ * **Low ____ Mass/(1)**\*

Answer 56

* **Oligo- or amenorrhea** with normal or low LH/FSH * **Galactorrhea** * Decreased libido - sexual dysfunction * Infertility * **Low Bone Mass/Osteoporosis**\* *Osteoporosis overtime happens dt decrease in estrogen*

Question 57

Treatment of Hyperprolactinemia **(1) Rx - (2)** High levels of prolactin → (1) to endocrine and (1) will be performed

Answer 57

**Dopamine Agonists** **Bromocriptine, Cabergoline** High levels of prolactin -\> referral to endocrine and an MRI will be performed

Question 58

Eval of Pituitary Mass - Pituitary Microadenoma * Differential Diagnosis of a Pituitary “mass” starts with _____ adenomas and extends to non-pituitary adenomas and also includes inf\_\_\_\_\_ diseases (not often reported as mass) * Always start with the ____ of the adenoma when evaluating pituitary masses. For m\_\_\_\_adenomas – evaluate for hyperfunctioning adenoma

Answer 58

* Differential Diagnosis of a Pituitary “mass” starts with pituitary adenomas and extends to non-pituitary adenomas and also includes infiltrative diseases (not often reported as mass) * Always start with the size of the adenoma when evaluating pituitary masses. For microadenomas – evaluate for hyperfunctioning adenoma

Question 59

Pituitary Microadenomas Functional and common (3) Functional (2)

Answer 59

**Prolactinoma, Acromegaly, ACTH secreting pituitary adenoma (Cushing's)** **LH/FSH or TSH secreting adenomas**

Question 60

Pituitary Macroadenoma Q1 - is this f\_\_\_\_\_? **Q2 - is this causing a ____ effect?** **(main difference)** Q3 - is this causing h\_\_\_\_pituitarism

Answer 60

Is this functional? **Is this causing a mass effect\*?** Is this causing hypopituitarism * Additional concerns with macroadenoma* * Is this tumor pressing on other things, is it causing destruction of normal pituitary to cause inadequate thyroid function?* * Main difference is worrying about mass effect – checking thyroid and cortisol levels asap!\** * Send to neurosurgeon!*

Question 61

Pituitary Mass Effects **(1)\*** **Need to see a (1)** **Red flag (1)**

Answer 61

**Bitemporal Visual Field Defects\*** **Neuro-ophthalmologist** **CSF rhinorrhea** (we worry about bacteria going up into CSF and causing meningitis)

Question 62

Hypopituitarism Causes target _____ failure 1. No (1) → Diabetes Insipidus 2. No (1) → amenorrhea/decreased libido 3. No (1) → failure to lactate 4. No (1) → short stature, hypoglycemia, mild anemia 5. No (1) → cold intolerance, poor memory, decreased energy 6. No (1) → Lack of well being, poor appetite, hypotension, low sodium

Answer 62

Target organ failure 1. No ADH → Diabetes Insipidus 2. No LH/FSH → amenorrhea/decreased libido 3. No PR → failure to lactate 4. No GH → short stature, hypoglycemia, mild anemia 5. No TSH → cold intolerance, poor memory, decreased energy 6. No ACTH → Lack of well being, poor appetite, hypotension, low sodium * If you have one of these will be called hypopituitarism* * If you have all of these pan-hypopituitarism*

Question 63

Causes of Hypopituitarism * _Congenital_: G\_\_\_\_ and dev\_\_\_\_\_\_\_ defects * _Tumors_: Pituitary M\_\_\_\_adenoma, Craniopharyngioma, other sella or parasella tumors M\_\_\_\_\_\_ deposition – breast, lung, others * _Inflammation/Infiltrative_: Sar\_\_\_\_, T\_, Hypophysitis, Histiocytosis X * _Vascular/Infarction:_ **Sh\_\_\_\_\_s**\*, Pituitary **A\_\_\_\_\_\_**\*\*, Parasellar Aneurysms, Trauma

Answer 63

* _Congenital_: Genetic and developmental defects * _Tumors_: Pituitary Macroadenoma, Craniopharyngioma, other sella or parasella tumors Metastatic deposition – breast, lung, others * _Inflammation/Infiltrative_: Sarcoid, TB, Hypophysitis, Histiocytosis X * _Vascular/Infarction:_ **Sheehan’s\***, Pituitary **Apoplexy\*\*,** Parasellar Aneurysms, Trauma

Question 64

ICI Hypophysitis Takeaway?

Answer 64

Immune checkpoint inhibitors used in RCC and melanoma are now causing a lot of hypophysitis AE of drug that activates autoimmunity in endocrine glands

Question 65

Causes of Hypopituitarism - Apoplexy Acute onset of symptoms referred to the pituitary gland secondary to a h\_\_\_\_\_\_\_ event (less likely can be secondary to a non-hemorrhagic event) * Head\_\_\_\_ with nausea, emesis, s\_\_\_\_ neck, fever * +/- ______ Field Deficit – can see BTH or a CN palsy * +/- Acute onset of H\_\_\_\_\_pituitarism * Acute secondary ad\_\_\_\_\_\_ insufficiency is most concerning hormone deficit and results in nausea, emesis, poor appetite, lightheadedness hyponatremia and hypotension

Answer 65

Acute onset of symptoms referred to the pituitary gland secondary to a hemorrhagic event (less likely can be secondary to a non-hemorrhagic event) * Headache with nausea, emesis, stiff neck, fever * +/- Visual Field Deficit – can see BTH or a CN palsy * +/- Acute onset of Hypopituitarism * Acute secondary adrenal insufficiency is most concerning hormone deficit and results in nausea, emesis, poor appetite, lightheadedness hyponatremia and hypotension *We worry about blood pooling and compressing structures -\> n/v, bilateral heminopsia, headache*

Question 66

Posterior Pituitary AVP Secretion * Posterior Pituitary: N\_\_\_\_\_\_ bodies are located in the Hypothalamus (2) * Ax\_\_\_\_\_\_ endings release hormones

Answer 66

* Posterior Pituitary: Neuronal bodies are located in the Hypothalamus (Supraoptic, Paraventricular) * Axonal endings release hormones

Question 67

ADH and Urine In the absence of Vasopressin (ADH), what happens to urine?

Answer 67

A large volume of dilute (hypotonic) urine is excreted (200-100cc/hr)

Question 68

Diabetes Insipidus * Presentation of \_\_\_\_uria * Evaluate for _____ diuresis (glucose, etc) * When the urine is found to be dilute (hypotonic) - the focus turns to (1) hormone Types of Polydipsia 1. **(1) =** Ingestion of excess volume of fluid 2. **(1) =** Reduced production/secretion of AVP 3. **(1) =** Enhanced metabolism of AVP 4. **(1) =** Reduced responsiveness to AVP

Answer 68

* Presentation of polyuria * Evaluate for osmotic diuresis (glucose, etc) * When the urine is found to be dilute (hypotonic) - the focus turns to hormone Types of Polydipsia 1. **Primary Polydipsia =** Ingestion of excess volume of fluid 2. **Central DI =** Reduced production/secretion of AVP 3. **Central DI =** Enhanced metabolism of AVP 4. **Nephrogenic DI =** Reduced responsiveness to AVP

Question 69

Diabetes Insipidus Etiology **Post\_\_\_ectomy** **Tumors (Cranio\_\_\_\_\_)** **Secondary (met\_\_\_\_\_\_)** **Granulomas like Sar\_\_\_\_\_\_** **L\_\_\_\_\_\_ hypophysitis** (autoimmune) * (1) = Destruction of ADH center alone * Destruction of ADH center + Destruction of hypothalamic Thirst center = can be \_\_\_\_\_

Answer 69

**Posthypophysectomy** **Tumors (Craniopharyngioma)** **Secondary (metastasis)** **Granulomas like Sarcoidosis** **Lymphocytic hypophysitis** (autoimmune) * Central DI = Destruction of ADH center alone * Destruction of ADH center + Destruction of hypothalamic Thirst center = can be Sarcoidosis

Question 70

Water Deprivation Test to Evaluate for DI =

Answer 70

Withhold water then give dose of **vasopressin → if urine osmolality goes up → Central DI** If they do not respond, refer to neuro for workup of nephrogenic DI

Question 71

Treatment of Central DI **Drug of Choice (1)\*** * V2 receptor selective, no V1 activity, so no vaso\_\_\_\_\_/B\_\_ concerns * Admin: (4) routes, poor absorption with (1) form so need to correct dosing, (2) routes for inpatient * Monitor for \_\_\_\_uria/th\_\_\_\_ and serum N\_\_ or os\_\_\_\_\_\_

Answer 71

**Desmopressin (ddAVP)** * V2 receptor selective, no V1 activity, so no vasoconstriction/BP concerns * Admin: (Nasal spray, PO, IV, SQ) routes, poor absorption with (PO) form so need to correct dosing, (IV, SQ) routes for inpatient * Monitor for polyuria/thirst and serum Na or osmolarity

Question 72

Diabetes and COVID takeaway?

Answer 72

People with diabetes 50% more likely to die from COVID-19 compared with no diabetes And COVID worsens Diabetes outcomes → triggers new onset Diabetes and more frequent and severe DKA

Question 73

Diabetes + Covid Mortality Increased mortality risk for diabetes patients with COVID-19 with * ______ age * ______ BMI * _____ sex

Answer 73

* Older age * Increased BMI * Male sex * 1 out of 3 people with diabetes and COVID-19 died at Montefiore March-May 2020* * Insulin treatment as a proxy for diabetes duration and obesity was predictive of mortality rather than HbA1c levels* * Further investigation of underlying mechanisms of mortality and inpatient glycemic control is needed* * COVID virus just caused such an intense form of hyperglycemia*